The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most ...patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes.
Patients with distal or middle third, T3–T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A—preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B—four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS).
A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively.
Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.
The relationship between central obesity and survival in community-dwelling adults with normal body mass index (BMI) is not well-known.
To examine total and cardiovascular mortality risks associated ...with central obesity and normal BMI.
Stratified multistage probability design.
NHANES III (Third National Health and Nutrition Examination Survey).
15,184 adults (52.3% women) aged 18 to 90 years.
Multivariable Cox proportional hazards models were used to evaluate the relationship of obesity patterns defined by BMI and waist-to-hip ratio (WHR) and total and cardiovascular mortality risk after adjustment for confounding factors.
Persons with normal-weight central obesity had the worst long-term survival. For example, a man with a normal BMI (22 kg/m2) and central obesity had greater total mortality risk than one with similar BMI but no central obesity (hazard ratio HR, 1.87 95% CI, 1.53 to 2.29), and this man had twice the mortality risk of participants who were overweight or obese according to BMI only (HR, 2.24 CI, 1.52 to 3.32 and 2.42 CI, 1.30 to 4.53, respectively). Women with normal-weight central obesity also had a higher mortality risk than those with similar BMI but no central obesity (HR, 1.48 CI, 1.35 to 1.62) and those who were obese according to BMI only (HR, 1.32 CI, 1.15 to 1.51). Expected survival estimates were consistently lower for those with central obesity when age and BMI were controlled for.
Body fat distribution was assessed based on anthropometric indicators alone. Information on comorbidities was collected by self-report.
Normal-weight central obesity defined by WHR is associated with higher mortality than BMI-defined obesity, particularly in the absence of central fat distribution.
National Institutes of Health, American Heart Association, European Regional Development Fund, and Czech Ministry of Health.
We demonstrate an integrated optical pressure sensing platform for multiplexed optofluidics applications. The sensing platform consists in an array of elastomeric on-side nanostructured membranes ...-effectively 2D photonic crystal- which present colour shifts in response to mechanical stress that alter their nanostructure characteristical dimensions, pitch or orientation. The photonic membranes are prepared by a simple and cost-effective method based on the infiltration of a 2D colloidal photonic crystal (CPC) with PDMS and their integration with a microfluidic system. We explore the changes in the white light diffraction produced by the nanostructured membranes when varying the pneumatic pressure in the microfluidics channels as a way to achieve a power-free array of pressure sensors that change their reflective colour depending on the bending produced on each sensor. The structural characterization of these membranes was performed by SEM, while the optical properties and the pressure-colour relation were evaluated via UV-Vis reflection spectrometry. Maximum sensitivities of 0.17 kPa
is obtained when measuring at Littrow configuration (θ
= -θ
), and close to the border of the membranes. The reflected colour change with pressure is as well monitorized by using a smartphone camera.
The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs.
This was a ...multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated.
A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months 95% confidence interval (CI) 4.8-14.1. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively.
Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201).
NCT01280201.
In order to evaluate the following potential mechanisms underlying atypical gaze following in autism, impaired reflexive gaze following, difficulty integrating gaze and affect, or reduced ...understanding of the referential significance of gaze, we administered three paradigms to young children with autism (
N
= 21) and chronological (
N
= 21) and nonverbal mental age (
N
= 21) matched controls. Children with autism exhibited impaired reflexive gaze following. The absence of evidence of integration of gaze and affect, regardless of diagnosis, indicates ineffective measurement of this construct. Reduced gaze following was apparent among children with autism during eye-tracking and in-person assessments. Word learning from gaze cues was better explained by developmental level than autism. Thus, gaze following may traverse an atypical, rather than just delayed, trajectory in autism.
Current body mass index (BMI) strata likely misrepresent the accuracy of true adiposity in older adults. Subjects with normal BMI with elevated body fat may metabolically have higher cardiovascular ...and overall mortality than previously suspected. We identified 4,489 subjects aged ≥60 years (BMI = 18.5 to 25 kg/m2 ) with anthropometric and bioelectrical impedance measurements from the National Health and Nutrition Examination Surveys III (1988 to 1994) and mortality data linked to the National Death Index. Normal weight obesity (NWO) was classified in 2 ways: creation of tertiles with highest percentage of body fat and body fat percent cutoffs (men >25% and women >35%). We compared overall and cardiovascular mortality rates, models adjusted for age, gender, smoking, race, diabetes, and BMI. The final sample included 1,528 subjects, mean age was 70 years, median (interquartile range) follow-up was 12.9 years (range 7.5 to 15.3) with 902 deaths (46.5% cardiovascular). Prevalence of NWO was 27.9% and 21.4% in men and 20.4% and 31.3% in women using tertiles and cutoffs, respectively. Subjects with NWO had higher rates of abnormal cardiovascular risk factors. Lean mass decreased, whereas leptin increased with increasing tertile. There were no gender-specific differences in overall mortality. Short-term mortality (<140 person-months) was higher in women, whereas long-term mortality (>140 person-months) was higher in men. We highlight the importance of considering body fat in gender-specific risk stratification in older adults with normal weight. In conclusion, NWO in older adults is associated with cardiometabolic dysregulation and is a risk for cardiovascular mortality independent of BMI and central fat distribution.
This is the first study that seeks to establish the prognostic value of circulating tumor cell (CTC) (determined by CellSearch system) in patients with stage III CRC.
Our results suggest that given ...the low number of CTC in patients with localized CRC and the particular pattern of metastatic dissemination in patients with CRC, it is likely that CTC does not have a prognostic role in this setting.
The prognostic role of circulating tumor cells (CTC) in early colorectal cancer (CRC) has not been determined yet. We evaluated the potential prognostic value of CTC in stage III CRC patients.
Prospective multicenter study of 519 patients with stage III CRC recruited between January 2009 and June 2010. CTC were enumerated with the CellSearch System after primary tumor resection and before the start of adjuvant therapy. A total of 472 patients were included in the analysis.
CTC ≥1, ≥2, ≥3 and ≥5 were detected in 166 (35%), 93 (20%), 57 (12%) and 34 (7%) patients, respectively. Median follow-up was 40 months. In the overall population, CTC ≥1 (disease-free survival (DFS): HR 0.97,P = 0.85; overall survival (OS): HR 1.03,P = 0.89), ≥2 (DFS: HR 1.07,P = 0.76; OS: HR 1.02,P = 0.95), ≥3 (DFS: HR 0.96,P = 0.87; OS: HR 0.74,P = 0.41) and ≥5 (DFS: HR 0.72,P = 0.39; OS: HR 0.48,P = 0.21) were not associated with worse DFS and OS. No clinicopathological characteristics were significantly associated with the presence of CTC. In patients with disease relapse, the proportion with CTC ≥1 was not significantly different between those with single versus multiple metastatic locations (37.9% versus 31.4%,P = 0.761). In the multivariate analysis, CTC ≥1 was not an independent prognostic factor for DFS (HR 0.97,P = 0.87) and OS (HR 0.96,P = 0.89).
CTC detection was not associated with worse DFS and OS in patients with stage III CRC. Given the scarcity of CTC in these patients, it is likely that CTC determined by CellSearch system does not have a prognostic role in this setting. However, a longer follow-up is needed.
In this document, the Inter-American Committee of Cardiovascular Prevention and Rehabilitation, together with the South American Society of Cardiology, aimed to formulate strategies, measures, and ...actions for cardiovascular disease prevention and rehabilitation (CVDPR). In the context of the implementation of a regional and national health policy in Latin American countries, the goal is to promote cardiovascular health and thereby decrease morbidity and mortality. The study group on Cardiopulmonary and Metabolic Rehabilitation from the Department of Exercise, Ergometry, and Cardiovascular Rehabilitation of the Brazilian Society of Cardiology has created a committee of experts to review the Portuguese version of the guideline and adapt it to the national reality. The mission of this document is to help health professionals to adopt effective measures of CVDPR in the routine clinical practice. The publication of this document and its broad implementation will contribute to the goal of the World Health Organization (WHO), which is the reduction of worldwide cardiovascular mortality by 25% until 2025. The study group's priorities are the following: • Emphasize the important role of CVDPR as an instrument of secondary prevention with significant impact on cardiovascular morbidity and mortality; • Join efforts for the knowledge on CVDPR, its dissemination, and adoption in most cardiovascular centers and institutes in South America, prioritizing the adoption of cardiovascular prevention methods that are comprehensive, practical, simple and which have a good cost/benefit ratio; • Improve the education of health professionals and patients with education programs on the importance of CVDPR services, which are directly targeted at the health system, clinical staff, patients, and community leaders, with the aim of decreasing the barriers to CVDPR implementation.
Although ultrafiltration membranes have been used for the separation of macromolecules and colloids from solutions, this process has a limited application in the removal of dyes present in coloured ...discharges of textile industry, as these typically have much lower molecular weight than the molecular cut-off of the membranes (MWCO). In the present work, we have evaluated the behaviour of a polysulfone ultrafiltration membrane in the removal of different dyes from aqueous solutions (Congo red, methyl green and amaranth). Different variables (tangential flow rate, concentration of dye and pH of the feed) were studied to determine their influence on the separation processes (permeate flux and rejection coefficient). The results show that Congo red is easily removed with a GR60PP membrane (MWCO = 25 kDa), whereas methyl green and amaranth show rejection coefficient values of approximately 25.78% and 13.85%, respectively, at neutral pH. Also, an interesting effect is observed for the rejection coefficient for methyl green at different pH values. In addition, several treatments were performed to the membrane so as to modify its surface, trying to improve the values obtained for permeate flux and rejection rate.
The aim of this paper is to focus attention on the methodology used to carry out geometric analyses, based on digital models, of the different construction stages that are juxtaposed in the most ...emblematic building of the three selected in the study, the Cathedral of Valencia. These analyses will be the basis for the subsequent modelling of the building in each of its historical periods. It is an extremely complex building which its works began in 1262. Over the centuries it has been accumulating extensions and reforms adapted to the new architectural styles of each era. In this communication, the methodology used for the collection of massive data in this complex building will be exposed, making special mention of the different equipment used in each case, the programming of tasks, their coordination and the digital models obtained. Likewise, the process of carrying out the geometric analyses of each of the construction stages will be exposed. Lastly, the results obtained will be presented taking into account the possible geometric and proportional links that the successive interventions have given rise to.
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